Recombinant EphB4-HSA Fusion Protein and Pembrolizumab, MK-3475

NCT03049618 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: 0S-16-8NCI-2017-00189P30CA014089
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

This phase IIa trial studies how well recombinant EphB4-HSA fusion protein and pembrolizumab work in treating patients with non-small cell lung cancer that has spread to other places in the body or head and neck squamous cell cancer that has come back or spread to other places in the body. Recombinant EphB4-HSA fusion protein may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of cancer cells to grow and spread. Giving recombinant EphB4-HSA fusion protein and pembrolizumab may work better in treating patients with non-small cell lung or head and neck squamous cell cancer.

Conditions

ALK Gene Mutation; BRAF Gene Mutation; EGFR Gene Mutation; Head and Neck Squamous Cell Carcinoma; Metastatic Head and Neck Carcinoma; Recurrent Head and Neck Carcinoma; Recurrent Non-Small Cell Lung Carcinoma; ROS1 Gene Mutation; Stage III Non-Small Cell Lung Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  Calculated based on the evaluable population of patients who received at least 1 dose of therapy. Overall response rate (ORR) is complete response (CR) + partial response (PR) recorded from study entry until disease progression based on RECIST v1.1 criteria. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

  Up to 22 months

Secondary Outcomes (4)

• Duration of Response

  Up to 22 months

• Number of Participants With Adverse Events

  Adverse events were collected from first dose of study treatment up to 30 days after last dose of treatment, up to 21 months (number of treatment given ranged from 1 cycle to 30 cycles).

• Overall Survival (OS)

  Up to 41 months

• Progression Free Survival (PFS)

  Up to 23 months

Other Outcomes (15)

• Association of Biomarker With Overall Response Rate - HPV Status

  Up to 22 months

• Association of Biomarker With Overall Response Rate - P16 Status

  Up to 22 months

• Association of Biomarkers With Overall Response Rate - EphrinB2 Status

  Up to 22 months

Study Arms (2)

Head and Neck Cancer Cohort

EXPERIMENTAL

Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Biological: Recombinant EphB4-HSA Fusion Protein

Non-Small Cell Lung Cancer Cohort

EXPERIMENTAL

Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Biological: Recombinant EphB4-HSA Fusion Protein

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Head and Neck Cancer Cohort; Non-Small Cell Lung Cancer Cohort

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Head and Neck Cancer Cohort; Non-Small Cell Lung Cancer Cohort

Recombinant EphB4-HSA Fusion Protein BIOLOGICAL

Given IV

Also known as: sEphB4-HSA

Head and Neck Cancer Cohort; Non-Small Cell Lung Cancer Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• One of the following:
• Locally advanced or metastatic non-small cell lung cancer that has progressed after at least 1 line of platinum based chemotherapy
• Patients may have received up to 2 prior lines of chemotherapy
• Patients with actionable alterations in EGFR/ALK/ROS1/BRAF must also have progressed after treatment with a tyrosine kinase inhibitor appropriate for their genetic alteration
• Untreated patients who refuse 1st line platinum based chemotherapy are also eligible
• Squamous cell carcinoma of the head and neck whose disease has progressed after at least 1 line of platinum based chemotherapy
• Patients may have received up to 2 prior lines of chemotherapy
• Untreated patients who refuse 1st line platinum based chemotherapy are also eligible
• Patients who relapse within 6 months of adjuvant cisplatin based concurrent chemoradiation, or neoadjuvant cisplatin based therapy can be considered eligible without an additional course of platinum chemotherapy for relapsed disease
• Patients may have either locally recurrent or distant metastatic disease
• Be willing and able to provide written informed consent/assent for the trial
• Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion after 2 cycles of therapy
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
• Absolute neutrophil count (ANC) \>= 1,500 /mcL

You may not qualify if:

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
• Has a known history of active TB (Bacillus tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to a previously administered agent
• Note: subjects with =\< grade 2 neuropathy are an exception to this criterion and may qualify for the study
• Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
• Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability; known brain metastases are considered active, if any of the following criteria is applicable:
• Brain imaging during screening demonstrates progression of existing metastases and/or appearance of new lesions compared to brain imaging performed at least 4 weeks earlier
• Neurological symptoms attributed to brain metastases have not returned to baseline
• Steroids were used for brain metastases within 28 days of randomization
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Has known history of, or any evidence of active, non-infectious pneumonitis

Sponsors & Collaborators

• University of Southern California: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Victoria Soto
• Organization: University of Southern California

victoria.soto@med.usc.edu

323-865-3441

Study Officials

• Jorge Nieva, MD

  University of Southern California

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2017
• First Posted: February 10, 2017
• Study Start: March 10, 2017
• Primary Completion: September 4, 2024
• Study Completion: September 4, 2024
• Last Updated: October 22, 2025
• Results First Posted: October 22, 2025

Record last verified: 2025-10

Locations

US (1)